The contribution of extrachromosomal DNA to genome plasticity in malaria parasites.
The contribution of extrachromosomal DNA to genome plasticity in malaria parasites.
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DOI：
10.1111/mmi.14632
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发表时间：
2021-04
影响因子：
3.6
通讯作者：
Kirkman, Laura A.
中科院分区：
文献类型：
--
作者：
Zhang, Xu;Deitsch, Kirk W.;Kirkman, Laura A.
尽管对药物和疫苗的开发和部署进行了大量投资，但由原生动物寄生虫恶性疟原虫引起的疟疾继续造成严重的发病率和死亡率。这种寄生虫的恢复能力的基础是其进行基因组修饰的非凡能力，从而为寄生虫种群提供了广泛的遗传变异性，从而加速了耐药性的选择并限制了大多数疫苗的功效。这种基因组可塑性植根于寄生虫用来维持基因组完整性的DNA修复机制，这一过程通过经典非同源末端连接的进化丧失而偏向于同源重组。 DNA 双链断裂的修复已被证明能够对抗原编码基因序列进行“改组”，从而大大增加抗原多样性，并使有助于耐药性的基因的拷贝数得以扩展。后一种现象被认为是导致几类抗疟疾药物耐药性上升的主要原因。在本期《分子微生物学》中，McDaniels 及其同事添加了疟疾寄生虫用来降低药物敏感性的另一种机制，证明恶性疟原虫可以维持扩大的耐药盒阵列作为稳定复制的环状染色体外 DNA，从而将基因组可塑性扩展到寄生虫的 14 条核染色体之外。
Malaria caused by the protozoan parasite Plasmodium falciparum continues to impose significant morbidity and mortality, despite substantial investment into drug and vaccine development and deployment. Underlying the resilience of this parasite is its remarkable ability to undergo genome modifications, thus providing parasite populations with extensive genetic variability that accelerates selection of drug resistance and limits the efficacy of most vaccines. This genome plasticity is rooted in the mechanisms of DNA repair that parasites employ to maintain genome integrity, a process skewed toward homologous recombination through the evolutionary loss of classical non-homologous end joining. Repair of DNA double strand breaks have been shown to enable “shuffling” of antigen encoding gene sequences to vastly increase antigen diversity and to enable copy number expansion of genes that contribute to drug resistance. The latter phenomenon has been proposed to be a major contributor to the rise of resistance to several classes of anti-malarial drugs. In this issue of Molecular Microbiology, McDaniels and colleagues add yet another mechanism that malaria parasites use to reduce drug susceptibility by demonstrating that P. falciparum can maintain expanded arrays of drug resistance cassettes as stably replicating, circular, extrachromosomal DNAs, thus expanding genome plasticity beyond the parasite’s 14 nuclear chromosomes.
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影响因子：
3.7
作者：
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DOI：
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